This proposal requests support for the continued investigation of the Q and T region class Ib genes and their products. These major histocompatibility complex antigens are similar in structure to the classical class I molecules; however, biological functions have yet to be established clearly. Our efforts focus on the structure/function of the Qa-1, TL, and Qa-2 molecules and the molecular regulation of th T18 and T23 genes. Direct evidence for mechanisms through which the classical class I molecules restrict recognition of antigen by T cells came from the proof that they bound endogenous peptides and the determination of amino acid sequences for these prptides. It is suspected but not proven that the Q and T region encoded molecules similarly bind peptides derived from self and foreign antigen. Our first aim is to isolate the Qa-1, TL, and Qa-2 molecules from cell lines and determine the amino acid sequence of peptides released from their antigen binding clefts. This line of investigation will 1) define what types of antigens can be presented by these class I molecules; 2) determine whether their functions are specialized or generalized like classical class I antigens; and 30 provide a foundation for more detailed structural analyses. We previously determined that the T23 gene encoded the Qa-1b molecule and our second aim addresses distinctive features of this protein. We will isolate the characterize an H-2S region gene designated Qsm responsible for a modification of Qa-1 that leads to alternative cell surface forma. We also will address mechanisms responsible for the rapid turnover of Qa-1 and dependence upon oligosaccharide for cell surface expression. Our third aim is to define regulatory elements responsible for the control of expression of the T18 and T23 genes. T18, which encodes TL, has a very restricted tissue distribution, while T23 which encodes Qa-1 has a more or less ubiquitous level of expression. Neither of these genes have in their 5' regions the consensus regulatory elements of classical class I genes. Thus, a delineation of the promoter/enhancer regions and transcription factors that bind to these elements will provide new information regarding tissue specific versus constitutive expression of class I genes. We have found that T18 has an unusual promoter and will dissect it further as part of this aim. We are confident that these proposed studies will answer pertinent and fundamental questions about the immune function of the Q and T region molecules and mechanisms that regulate their expression and further our understanding of the biological roles of class I molecules in general.